A case of KMT2A-SEPT9 fusion-associated acute megakaryoblastic leukemia

Abstract

Acute megakaryoblastic leukemia (AMKL) constitutes ∼5%-15% of cases of non-Down syndrome AML in children, and in the majority of cases, chimeric oncogenes resulting from recurrent gene rearrangements are identified. Based on these rearrangements, several molecular subsets have been characterized providing important prognostic information. One such subset includes a group of patients with translocations involving the KMT2A gene, which has been associated with various fusion partners in patients with AMKL. Here we report the molecular findings of a 2-yr-old girl with AMKL and t(11;17)(q23;25) found to have a KMT2A-SEPT9 fusion identified through targeted RNA sequencing. A KMT2A-SEPT9 fusion in this subset of patients has not previously been reported.

Trial registration: ClinicalTrials.gov NCT01775072.

Keywords: acute megakaryocytic leukemia; acute myeloid leukemia; leukemia.

Figure 1.

(A) Chromosome analysis reveals a balanced chromosome translocation between Chromosomes 11 and 17—that is, t(11;17)(q23;q25) (arrows). (B) FISH analysis with a KMT2A break-part probe set (Abbott Molecular) shows a split KMT2A signal pattern—that is, t(11;17). The 5′ KMT2A and 3′ KMT2A were labeled with green and orange, respectively. (C) Schematic illustration of the protein structure, bidirectional RNA sequencing reads, and transcript sequence of the KMT2A (NM_005593)–SEPT9 (NM_006640) in-frame fusion product detected by Archer FusionPlex with exons 1–7 of KMT2A fused to exons 2–9 of SEPT9.